ION-CHANNEL FORMATION BY SYNTHETIC ANALOGS OF STAPHYLOCOCCAL DELTA-TOXIN

Ion channel formation by three analogues of staphylococcal delta-toxin , an amphipathic and alpha-helical channel-forming peptide, has been e valuated by measurement of ionic currents across planar lipid bilayers . Replacement of beta-branched, hydrophobic residues by leucine and mo vement of a tryptophan residue from the hydrophilic to the hydrophobic face of the helix does not significantly alter ion channel activity. Removal of the N-terminal blocking group combined with the substitutio n of glycine-10 by leucine changes the single channel properties of de lta-toxin, without altering macroscopic conductance/voltage behaviour. Truncation of the N-terminus by three residues results in complete lo ss of channel-forming activity. These changes in channel-forming prope rties upon altering the peptide sequence do not mirror changes in haem olytic activity. The results lend support to the proposal that channel formation and haemolysis are distinct events. Channel properties are discussed in the context of a model in which the pore is formed by a b undle of approximately parallel transbilayer helices.